There is a critical need for improved treatments for pain associated with burn injury. Pain control after burn injury is a major challenge from the initial point of care through rehabilitation. The overall objective of this project is to develop a easily-applied topical delivery system based on analgesic microparticles that can be used for treatment of pain associated with deep partial thickness burns. One of the critical barriers to progress is that current therapies are administered systemically with concomitant side effects in addition to often insufficient pain relief - no topical treatments are available to treat burn pain This new topical treatment approach is designed to target pain at the source, lowering usage of systemic opioids or other treatments, thus reducing unwanted side effects associated with the current systemic treatments and enhancing the effectiveness of burn pain relief. A key focus of this research is to determine which microparticle topical delivery system has the highest potential for burn pain relief. The application of peripherally-acting analgesics has been designed to provide effective, simple-to-use, easily and painlessly applied treatment of pain associated with burn injury. This topical microparticle delivery technology has the potential to lead to a marketable product and the proposed technology will improve current treatment methodologies for burn injury and pain. The first specific aim is to incorporate therapeutic agents into the topical delivery system. The second aim is to evaluate drug release characteristics ex vivo using a bioartificial dermis system. The third specific aim is to select th formulation for in vivo testing utilizing a team of clinical burn and scientific pain experts. The fourth specific aim is to evaluate the efficacy of the optimized delivery system in vivo using a rodent burn model. The resulting product is being designed to be a unique topical delivery system that can be used to painlessly apply analgesic treatment for burn pain. The impact of this research is to help the millions of victims, many of whom are children and wounded warriors, who have debilitating acute and chronic pain resulting from burns.